The goal of this program is to systematically explore the influence of physicochemical properties of size, composition, surface lability as well as charge, density, and activity of engineered nanomaterials (ENMs). The goal of this project is to define the effect of these physical/chemical properties on how ENMs interact with the intact organism, including specific target organs and specific cell types within the target organs. We will focus one ofthe major classes of ENMs, the high aspect ratio nanomaterials (HARNMs), including single wall carbon nanotubes (SWNTs) and nanowires (NWs) of various lengths. The importance of size (diameter and length) and coatings (silica as one example) to affect toxicity, retention and translocation will be assessed. HARNM with differing physical/chemical property described above will be employed in a series of systematic examinations of absorption and distribution following inhalation/ingestion experiments. Primary and secondary target organ responses will be monitored, and the influence of HARNM exposure In a model of allergy will be assessed. The overall hypothesis Is that differences in composition, size, diameter and surface coating of HARNMs will modulate the in vivo uptake, distribution and biologic effects of HARNMs in a rat model. This hypothesis will be addressed in four specific aims that will determine the effect of HARNM on 1) deposition, retention and distribution to various organs; 2) respiratory system cytotoxicity, inflammation and airway remodeling; 3) oxidative stress in the respiratory system; and 4) exacerbation of ainway hyperresposiveness in a sensitive model. We will address these aims using a transdisciplinary approach that combines inhalation toxicology, chemistry, histopathology, high resolution imaging and novel methodologies developed at UC Davis that uniquely position us to successfully address the biological effects of these materials. The long term goal is to identify features of these materials that reduce their toxicity and biological effects. RELEVANCE (See instnjctions); To develop and evaluate techniques and approaches to assess the potential disease burden associated with exposures to ENMs. The goal of Project 2 is to define exposure effects of high aspect ratio nanomaterials (single walled carbon nanotubes and nanowires) in an in vivo inhalation model that includes airways hyperresonsiveness.